Clinical and molecular findings in nine new cases of tetrasomy 18p syndrome: FISH and array CGH characterization

Wafa Slimani,Hanene Hannachi,Ali Saad,Soumaya Mougou-Zerelli,Fatma-Zohra Chioukh,Hela Ben Khelifa,Sarra Dimassi,Nesrine Jammali,Molka Kammoun,Afef Jelloul,Sarra Bouslah,Damien Sanlaville

doi:10.1186/s13039-019-0414-8

Abstract

BackgroundSmall Supernumerary Marker Chromosomes (sSMC) are rare chromosomal abnormalities, which have abnormal banding arrangement and take many shapes. Several disorders have been correlated with sSMC presence. The aim of this study is to characterize the sSMC derived from chromosome 18 by Fluorescence in situ hybridization (FISH) and Array Comparative Genomic Hybridization (aCGH).ResultsNine children with dysmorphic features have been investigated. They have these features in common: a triangular face, low-set ears, a large mouth with a thin upper lip, and a horizontal palpebral fissure. Epicanthus and strabismus were present in two patients. In addition, we have noticed microcephaly and mental and/or developmental delay with low birth weight. However, two patients had standard birth weight; one patient had hypospadias; two had skin problems; and three showed different congenital heart defects. One patient had corpus callosum hypoplasia. Systematic karyotype analysis revealed a de novo supernumerary chromosome. Array CGH showed a gain in copy number on the short arm of chromosome 18 in the nine cases. In one case, the sSMC seemed to be in mosaic. The breakpoints of the marker were identified using aCGH and FISH. Thus, the sSMC led to 18p tetrasomy with approximately 14 Mb lengths, between 364344 and 14763575 based on the human genome version 18.ConclusionsThese results have been completed by FISH in order to ascertain the shape of the sSMC. Our results confirm the uniqueness and particularity of the iso18p syndrome on the phenotypic as well as on the genetic level.

Highlights

Small Supernumerary Marker Chromosomes are rare chromosomal abnormalities, which have abnormal banding arrangement and take many shapes
(2019) 12:5 (OMIM 601803), Cat eye syndrome (OMIM 115470), isodicentric 15q and isochromosome18p (i18p) (OMIM: # 614290). The latter is a rare chromosomal abnormality that results in 18p tetrasomy and appears to be one of the most frequent isochromosomes observed in humans with a prevalence of 1/180000 in live born children [5, 6]
Patients Nine children were referred to our department of Cytogenetics and Biology of Reproduction to explore genetic origin of their developmental delay and/or intellectual disability and dysmorphic features

Summary

Introduction

Small Supernumerary Marker Chromosomes (sSMC) are rare chromosomal abnormalities, which have abnormal banding arrangement and take many shapes. Small Supernumerary Marker Chromosomes (sSMC) are rare chromosomal abnormalities, which can take different shapes and have abnormal banding pattern. This makes them hardly identifiable and ambiguously characterized using only conventional karyotype. (OMIM 601803), Cat eye syndrome (OMIM 115470), isodicentric 15q and isochromosome18p (i18p) (OMIM: # 614290) The latter is a rare chromosomal abnormality that results in 18p tetrasomy and appears to be one of the most frequent isochromosomes observed in humans with a prevalence of 1/180000 in live born children [5, 6]

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